An account given on MS by one of the best neurologists doctor in DubaiPosted by advanceseo on November 28th, 2019 The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year. Herein, we go back to the basics to understand the immunopathophysiology of MS to gain insights in the development of new improved drug treatments. We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS. In the early 1900s, only a few cases of multiple sclerosis diagnosis (MSD) were reported, which quickly became a common occurrence for admission to neurological wards. Today, MS accounts over 2.5 million affected individuals with an estimated cost of US–3 billion per annum. The distribution of MS varies according to geographic location. For example, the further north or south from the equator the higher the prevalence of MS; countries that lie on the equator have extremely low prevalence compared to Scotland, Norway, and Canada. The prevalence of MS has increased progressively over time with 30/100,000 diagnosed in 2008 to 33/100,000 diagnosed in 2013 globally. In fact, in a Norwegian cohort over 53 years (1961–2014), the prevalence increased from 20 to 203/100,000 and the incidence increased from 1.9 to 8/100,000. It is possible that the increase in prevalence is due to improved diagnostic procedures and reporting and changes in lifestyle (lack of vitamin D and increased smoking). MS is commonly diagnosed between 20 years and 40 years of age although it can affect younger and older individuals, and most commonly affects those with a genetic predisposition (major histocompatibility complex (MHC) class II phenotype, human leukocyte antigen (HLA)-DR2 and HLA-DR4 most commonly affected). In fact, the incidence of MS is increased 10-fold in monozygotic twins as compared to siblings of patients with MS. In addition, viral infections can trigger disease where parts of the virus mimics that of the myelin sheath . Although usually not life-shortening, MS is a chronic neurological disease often interfering with life and career plans of an individual . MS is categorized into 4 distinct types, primarily based on its clinical course, which are characterized by increasing severity: (a) Relapsing/remitting MS (RRMS), the most common form, affecting 85% of all MS patients which involves relapses followed by remission; (b) secondary progressive MS (SPMS), which develops over time following diagnosis of RRMS; (c) primary progressive MS (PPMS) affecting 8–10% of patients, noted as gradual continuous neurologic deterioration; and (d) progressive relapsing MS (PRMS) the least common form (less than 5%). MS leads to a wide range of symptoms with various severity involving different parts of the body. MS diagnosis is mainly clinically based however, magnetic resonance imaging (MRI) assists in diagnosis . As such, examination of the cerebrospinal fluid (CSF) and visual induced potentials with MRI can assist in confirming the clinical suspicion of MS . MS symptoms and disease progression are varied, with some individuals experiencing little disability while most (up to 60%) require a wheelchair 20 years from diagnosis. Although best neurologist treatments in Dubai against are able to decrease the relapse rate in RRMS, the prevention of long-term effects remains a problem; medications for progressive forms of MS are also limited in their efficacy. Hence, new improved drugs are required to effectively treat MS. One of the major pathophysiological mechanisms of MS involves autoreactive T cells, primarily T helper (Th)-1 CD4+ T cells and Th17 cells leading to cytokine secretion and activation of an inflammatory cascade resulting in demyelination within the brain and spinal cord and axonal damage; autoreactive antibodies cannot be discounted. Indeed, MS is generally known as a chronic autoimmune disorder of the central nervous system (CNS) . MS causes breakdown of the blood brain barrier (BBB) leading to migration of immune cells (macrophages, T cells, B cells) and secretion of pro-inflammatory cytokines and chemokines which induces inflammation, formation of sclerotic plaques (lesions), demyelination and neurodegeneration . MS lesions may form in any location of the CNS white matter or in grey matter, often leading to physical disability and sometimes, decline in cognitive ability [16,18]. It is therefore, conceivable to target immune cells and their products in order to prevent tissue damage by modulating inflammation while reducing potential side effects such as global immunosuppression . The major constituents of the myelin sheath in which autoreactive T cells and antibodies recognize, include, myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) and proteolipid protein (PLP). Clinic at a glance
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